The evidence to date shows that interstitial procollagens are glycoproteins. Since the role of glycosylation in general is not understood, we propse to study in detail the glycosylation of the propeptide domains of chick interstitial procollagens Type I, II and III. These studies will include the isolation, purificaiton and characterization of procollagen, propeptides, glycopeptides, oligosaccharide units and their lipid intermediates. To assess the ability of oligosaccharide units to function in the processing of procollagen, potential inhibitors of glycosylation will be used. This information will be applied to the development of a coherent model for the role of propeptide glycosylation in the control of collagen synthesis and/or secretion. In addition, similar studies will be performed using fibroblasts from normal human sources and those from patients with osteogenesis imperfacta. Since there is a reported defect in Type I procollagen propeptide glycosylation in the cells from a single patient, we will use the expertise developed in our laboratory to study this defect in detail. We will also obtain cells from other patients suffering from this disorder in order to confirm the prevalence of this defect. If the defect can be pinpointed, it may be possible to design a prenatal test for osteogenesis imperfecta using cells obtained froam pregnant women by amniocentesis.